Neoadjuvant immunotherapy in resectable hepatocellular carcinoma: A meta-analysis of the current evidence

doi:10.5306/wjco.v16.i10.110511

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World Journal of Clinical Oncology

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Meta-Analysis

World J Clin Oncol. Oct 24, 2025; 16(10): 110511
Published online Oct 24, 2025. doi: 10.5306/wjco.v16.i10.110511

Neoadjuvant immunotherapy in resectable hepatocellular carcinoma: A meta-analysis of the current evidence

Ottavia Cicerone, Barbara Oliviero, Stefania Mantovani, Laura Maiocchi, Valentina Ravetta, Francesca Berton, Salvatore Corallo, Alessandro Vanoli, Marcello Maestri

Ottavia Cicerone, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia 27100, Italy

Barbara Oliviero, Stefania Mantovani, Department of Translational and Clinical Research, Division of Molecular Medicine, Laboratory of Clinical Immunology, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy

Laura Maiocchi, Infectious Diseases 1 Unit, Fondazione IRCCS Policlinico S. Matteo, Pavia 27100, Italy

Valentina Ravetta, Department of Surgery, Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy

Francesca Berton, Department of Diagnostic Imaging, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy

Salvatore Corallo, Department of Internal Medicine and Medical Therapy - Unit of Oncology, University of Pavia - Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy

Alessandro Vanoli, Department of Molecular Medicine- Anatomic Pathology Unit, University of Pavia - Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy

Marcello Maestri, General Surgery Unit I - Liver Service, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy

Author contributions: Cicerone O contributed to the concept and design of the study, the meta-analysis and the writing of the original draft; Oliviero B, Mantovani S, Maiocchi L, Ravetta V and Berton F contributed to data curation and reference screening; Corallo S and Vanoli A contributed to the review and editing of the manuscript; Maestri M contributed to the concept and design of the study, the meta-analysis, the manuscript review and editing and the project administration.

Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.

PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Marcello Maestri, MD, PhD, Professor, General Surgery Unit I - Liver Service, Fondazione IRCCS Policlinico San Matteo, P.le Golgi 19, Pavia 27100, Italy. m.maestri@smatteo.pv.it

Received: June 10, 2025
Revised: June 25, 2025
Accepted: September 11, 2025
Published online: October 24, 2025
Processing time: 138 Days and 16.2 Hours

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. Despite improvements in surgical techniques and systemic therapies, long-term outcomes after liver resection are limited by high recurrence rates. While adjuvant strategies have shown limited benefit, the role of neoadjuvant immunotherapy in resectable HCC is still under investigation.

AIM

To assess the efficacy, feasibility, and safety of neoadjuvant immunotherapy in resectable HCC through a meta-analysis of current literature.

METHODS

A systematic search was conducted across PubMed, Web of Science, EMBASE, Cochrane Library, and Scopus for studies published in the past five years evaluating neoadjuvant immunotherapy in resectable HCC. Primary endpoints included major pathological response (MPR), pathological complete response (pCR), overall response rate (ORR), resection rate, and grade 3-4 treatment-related adverse events (TRAEs). A random-effects meta-analysis was conducted using log odds ratios (ORs) and pooled event rates were calculated to provide absolute estimates of clinical endpoints.

RESULTS

Twelve studies were included in the final analysis. The pooled ORs were 0.28 (95%CI: 0.19-0.41) for MPR, 0.54 (95%CI: 0.25-1.14) for ORR, 0.26 (95%CI: 0.11-0.66) for pCR, 5.37 (95%CI: 2.70-10.66) for resection rate, and 0.33 (95%CI: 0.22-0.50) for grade 3-4 TRAEs. Corresponding pooled event rates were 19% for MPR, 35% for ORR, 22% for pCR, 81% for resection feasibility, and 19% for severe TRAEs.

CONCLUSION

Neoadjuvant immunotherapy appears to be a feasible and safe approach in patients with resectable HCC, achieving moderate pathological responses and high resection rates.

Keywords: Hepatocellular carcinoma; Neoadjuvant immunotherapy; Immune checkpoint inhibitors; Liver resection; Resectable hepatocellular carcinoma; Preoperative treatment

Core Tip: This meta-analysis evaluates the efficacy and safety of neoadjuvant immunotherapy in resectable hepatocellular carcinoma (HCC). Pooled data suggest that this approach is feasible, with moderate pathological response rates and high resection feasibility, without a significant increase in severe toxicities. Although evidence is still limited, early findings support further investigation in prospective trials to define optimal treatment strategies and identify biomarkers predictive of response. Neoadjuvant immunotherapy may represent a promising strategy to improve surgical outcomes and reduce early recurrence in resectable HCC.